This research proposal is directed at elucidating the role of receptors in the subcellular mechanism of action of glucocorticoid hormones. Four related lines of inquiry will be pursued: 1) the ontogeny of the receptor system, analyzing the fetal development of receptors in relation to the appearance of hormone expression; 2) a comparative study of adult receptors in three critical glucocorticoid target organs -liver, kidney and thymus; 3) an investigation into possible pharmacological applications of receptor-steroid interactions; and 4) an analysis of the relationships of receptors and hormone effects as manifested by enzyme induction in vitro. Most studies will utilize the rat as the experimental animal, however monkey and human tissue will also be investigated. Target organs to be scrutinized will be liver, kidney and thymus, all of which are known to contain glucocorticoid receptors. A multiphasic experimental design is planned, subjecting several different but related aspects of the receptor mechanism to investigation. It is hoped that the interrelationships developed by this approach will significantly add to our understanding of the hormonal basis of cell regulation. BIBLIOGRAPHIC REFERENCES: M.E. Wolff, D. Feldman, P. Catsoulacos, J.W. Funder, C. Hancock, Y. Amano, and I.S. Edelman. Steroidal 21-diazo ketones: Photogenerated corticosteroid receptor labels. Biochemistry 14:1750-1759, 1975. D. Feldman and C. Couropmitree. Intrinsic mineralocorticoid agonist activity of some non-steroidal anti-inflammatory drugs: a postulated mechanism for sodium retention. J. Clin. Invest. 57:1-7, 1976.